Hemoglobin variants shape the distribution of malaria parasites in human populations and their transmission potential

Abstract : Hemoglobin variants C and S protect against severe malaria but their influence on parameters not directly linked to disease severity such as gametocyte carriage and infection chronicity is less well understood. To assess whether these infection-related phenotypes depend on the host hemoglobin genotype, we followed 500 Malian individuals over 1-2 years and determined their parasitological status during monthly visits and incidental clinical episodes. While adults heterozygous for hemoglobin S mutation were less often parasitemic compared to AA adults (odds ratio [OR] 0.50 95% confidence interval [CI] 0.31-0.79, P = 0.003), schoolchildren (but not toddlers or adults) with AC genotype carried parasites, including gametocytes, more often than their AA counterparts (OR 3.01 95% CI 1.38-6.57, P = 0.006). AC children were also likelier to be parasite-positive during the dry season, suggesting longer infections, and were more infectious in mosquito skin feeding assays than AA children. Notably, AC school-aged children, who comprise ~5% of the population, harbor a third of infections with patent gametocytes between May and August, when transmission transitions from very low to intense. These findings indicate that schoolchildren with hemoglobin C mutation might contribute disproportionately to the seasonal malaria resurgence in parts of West Africa where the HbC variant is common. Plasmodium falciparum infections can have diverse clinical presentations, even within the same person over time 1 , and this might impact the potential for onward transmission of the parasite. For example, individuals with asymptomatic infection can carry chronic parasitemia without seeking treatment and might remain infectious to mosquitoes for long periods of time. Consequently, identifying and addressing factors involved in frequent or long-lasting parasite carriage can be important to malaria elimination and control strategies that aim to reduce human-to-mosquito transmission. Here, we assessed whether two hemoglobinopathies, hemoglobin (Hb) S and HbC traits (AS and AC genotypes, respectively), that are frequent in sub-Saharan Africa 2,3 can influence parasite carriage and transmission. These two hemoglobin variants have been associated with protection against severe malaria syndromes in numerous epidemiological studies 4 , and mechanistic hypotheses proposed to explain this protection include impaired blood stage parasite development 5-7 , reduced cytoadherence of infected red blood cells 8,9 , which is linked to the redox imbalance of hemoglobinopathies and its effects on the export of parasite-encoded proteins 10,11 , tolerance to malaria infection related to heme catabolism by heme oxygenase-1 12 , or accelerated acquisition of immunity 13-15. Life-threatening episodes, however, represent only a small proportion of falciparum
Keywords : Malaria infection
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Bronner Gonçalves, Issaka Sagara, Mamadou Coulibaly, Yimin Wu, Mahamadoun Assadou, et al.. Hemoglobin variants shape the distribution of malaria parasites in human populations and their transmission potential. Scientific Reports, Nature Publishing Group, 2017, 7 (1), ⟨10.1038/s41598-017-14627-y⟩. ⟨inserm-01980936⟩

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